Submissions for variant NM_001199753.2(CPT1C):c.55G>A (p.Ala19Thr)

gnomAD frequency: 0.00001  dbSNP: rs1317849272

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000819923	SCV000960610	uncertain significance	Hereditary spastic paraplegia 73	2018-10-05	criteria provided, single submitter	clinical testing	In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with CPT1C-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change replaces alanine with threonine at codon 19 of the CPT1C protein (p.Ala19Thr). The alanine residue is weakly conserved and there is a small physicochemical difference between alanine and threonine.
Ambry Genetics	RCV004029019	SCV004849774	uncertain significance	not specified	2024-01-04	criteria provided, single submitter	clinical testing	The c.55G>A (p.A19T) alteration is located in exon 3 (coding exon 1) of the CPT1C gene. This alteration results from a G to A substitution at nucleotide position 55, causing the alanine (A) at amino acid position 19 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV004029019	SCV005186006	uncertain significance	not specified	2024-05-02	criteria provided, single submitter	clinical testing	Variant summary: CPT1C c.55G>A (p.Ala19Thr) results in a non-conservative amino acid change located in the Carnitine O-palmitoyltransferase, N-terminal domain (IPR032476) of the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 1.2e-05 in 251306 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.55G>A in individuals affected with Hereditary Spastic Paraplegia 73 and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 662312). Based on the evidence outlined above, the variant was classified as uncertain significance.